High Potency Proton Pump Inhibitor Versus Vonoprazan in Helicobacter pylori Triple Therapy

The price of vonoprazan in the United States, as with many newly introduced drugs, is currently high. Here, we examined the cost-effectiveness of vonoprazan clarithromycin triple therapy for treatment of Helicobacter pylori in the United States. We compared cure rates and total treatment costs to achieve ≥ 90% cure with either vonoprazan or proton pump inhibitor (PPI) triple therapy.

We simulated a theoretical population and compared 4 scenarios comparing vonoprazan 20 mg twice daily or esomeprazole 40 mg twice daily. These included: (1) empiric vonoprazan versus esomeprazole clarithromycin triple therapy, (2) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy, (3) empiric vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy, and (4) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy. The prevalence of clarithromycin resistance was estimated at 30%. Cure rates were based on the H. pylori treatment nomogram and drug costs on U.S. 2025 retail prices (i.e., $50 for PPI and $960 for vonoprazan triple therapy).

With 30% resistance, susceptibility-based therapy was the most effective (cure rate 92%). With empiric therapy, the cure rate with vonoprazan was higher than esomeprazole (88% vs. 77%) but overall costs increased 2.4-5.2 times. The cost per 1000 patients receiving vonoprazan was approximately $1000,000 versus $50,000 for esomeprazole. The least expensive, highly effective scenario was empiric esomeprazole triple therapy with treatment failures receiving bismuth quadruple therapy.

Any treatment advantage of vonoprazan over PPI in clarithromycin triple therapy is restricted to those with clarithromycin resistance. Vonoprazan triple therapies cost 2 to 5 times more than a high potency PPI with small gains in cure rates. For susceptible infections, triple therapy using a high potency PPI should be preferred, and the most cost-effective strategy is to reserve vonoprazan for refractory cases.